Significant Improvement of Hippocampus in Chronic Unpredictable Mild Stress Rats by Ethyl Acetate Extract of Taxus chinensis (Pilg.) Fruit: A New Functional Discovery of a Natural Product

Abstract Background: Depression is a neuroimmune disorder marked by inflammation in the cerebral cortex and hippocampus. Taxus Chinensis (Pilg.)Fruit is a natural product known for its anti-inflammatory effects. However, limited research exists on the antidepressant mechanisms of the ethyl acetate extract from Taxus chinensis (Pilg.) fruit (TCFE). Objective: This research primarily investigates the antidepressant mechanism of TCFE, focusing on its neuroprotective effects against anxiety and depression-like behaviors induced by chronic unpredictable mild stress (CUMS) in rats. Materials and Methods: A depression model was created using CUMS over a period of 3 weeks. Following this, rats in the TCFE group received TCFE orally at a dosage of 200 mg/(kg·d) for 4 weeks. Nissl staining was employed to examine the pathological changes in the hippocampus. Immunofluorescence method was used to detect the expression of Iba-1 in hippocampal microglia and the expression of NLRP3-related protein in hippocampus. In addition, to strengthen our in vivo findings, we conducted in vitro experiments on LPS-stimulated BV2 microglial cells. Finally, ultraperformance liquid chromatography-electrospray ionization mass spectrometry for precise component analysis using compound standards. Results: The TCFE treatment increased the body weight of rats, reduced the depression-like behavior of rats, regulated inflammatory factors in serum and hippocampus, reduced neuronal cell damage in hippocampus, improved the morphology of BV2 cells, reduced the activation of BV2 cells, and inhibited NLRP3 activation. Conclusions: Our results for the first time demonstrated that the TCFE has antidepressant effect, which has clinical application value and is worthy of further research and in-depth exploration.